The integration of newer agents into neoadjuvant therapy.

The overall prognosis for N2 non-small cell lung cancer treated by surgical resection alone is dismal. At this stage, the disease is systemic, and the presence of occult micrometastases leads to relapse in the majority of cases. Progress against the disease therefore requires a multimodality approach involving chemotherapy, radiotherapy, and surgery. At least two randomized trials have demonstrated that cisplatin-based induction chemotherapy before surgery substantially improves median and 5-year survival compared with surgery alone. Induction chemotherapy has an equally impressive effect when it precedes definitive thoracic radiotherapy. In both settings, cisplatin-based combinations can achieve cure in certain stage IIIA patients. Attaining complete resection and downstaging N2 disease are useful surrogates for long-term survival. One focus for future research is the earlier stages of disease, in which induction chemotherapy also may have a role. Another challenge is to integrate new active agents, such as docetaxel, into the neoadjuvant setting, and trials of either a cisplatin or a carboplatin plus docetaxel regimen are under way. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse and, hence, those in greatest need of chemotherapy.